The US Food and Drug Administration (FDA) has approved rituximab (Rituxan) for use in the first-line treatment of patients with diffuse large B-cell, CD20-positive non-Hodgkin’s lymphoma, in combination with CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone) or other anthracycline-based chemotherapy regimens. Rituximab has previously been approved as a single agent for use in relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s lymphoma.
“Diffuse large B-cell lymphoma can be fatal within as little as 6 months to 2 years without aggressive treatment,” said Sandra J. Horning, md, chair, lymphoma group for the Eastern Cooperative Oncology Group. “With this approval, Rituxan in combination with chemotherapy becomes the first FDA-approved treatment to improve survival for patients with this type of non-Hodgkin’s lymphoma since the introduction of the CHOP chemotherapeutic regimen more than 25 years ago.”
An estimated 360,000 Americans have non-Hodgkin’s lymphoma (NHL) and more than 58,000 new cases are diagnosed annually. Diffuse large B-cell lymphoma (DLBCL), an aggressive subtype of NHL, divides and multiplies rapidly in the body, and if left untreated, can be fatal. However, early diagnosis and treatment can improve chances of long-term survival. Of those diagnosed with NHL, about 50% have an aggressive form of the disease, the most common type being DLBCL. The other 50% of patients have a slow-growing but usually incurable or indolent form of the disease, of which the most common type is follicular lymphoma.
The FDA approval was based on efficacy and safety data from three randomized, controlled, multicenter studies of rituximab in combination with CHOP (R-CHOP) or other anthracycline-based chemotherapy induction regimens in 1,854 previously untreated patients with DLBCL. With 2 years of follow-up, more patients were alive in the rituximab-containing vs control arms for each study. In one of the studies with 5 years of follow-up (the Group d’Etude des Lymphome d’Adulte, or GELA, trial), R-CHOP improved overall survival by 47% compared to CHOP alone (hazard ratio = 0.68, or a 32% decrease in the risk of death).
The studies included in the submission to the FDA were GELA/LNH 98-5, E4494 (a National Cancer Institute-sponsored Intergroup trial led by the Eastern Cooperative Oncology Group), and MInT (MabThera International Trial M39045). Rituximab is known as MabThera in Europe.